Abstract
Purpose: :
The outcome of corneal allografts in vascularized "high risk" recipients is dismal. We hypothesize that independent of early T cell priming, the increased early innate inflammatory microenvironment in high risk corneal recipients enhances T cell recruitment and is responsible for the increased rate of graft rejection.
Methods: :
To study the effects of early innate inflammatory responses, orthotopic allogeneic corneal grafts were performed in non high risk and high risk vascularized Rag –/– recipients that lack T and B cells (Balb/c to Rag –/– C57BL/6). Twenty–two days after corneal grafting 1x106 purified T cells from EGFP transgenic mice were adoptively transferred by IV tail injection. Graft survival was documented and recruitment of EGFP positive T cells was monitored at different time points by in vivo fluorescent stereomicroscopy.
Results: :
Corneal allografts performed in non high risk and high risk Rag –/– recipients survived indefinitely. Accepted allografts in non high risk Rag –/– that received T cells continue to survive up to twenty days after adoptive transfer. A transient accumulation of EGFP positive T cells was observed in the host bed and graft, but resolved by day 10. In contrast, accepted allografts in high risk Rag –/– succumbed to rejection 7 days after the adoptive transfer of T cells. Corneal allograft rejection correlated with the increased recruitment and accumulation of EGFP positive T cells in the graft.
Conclusions: :
The presence of T cells immediately after transplantation is required for the rejection of non high risk and high risk orthotopic corneal allografts. However, in the absence of T cells only high risk corneal allografts are "immunologicaly marked" and can be later recognized by allo–antigeneic T cells. These results confirm our hypothesis that early innate inflammatory signals regulate adaptive T cell responses and can be an important mechanism that explains the dismal outcome in high risk corneal graft recipients.
Keywords: transplantation • inflammation • immunomodulation/immunoregulation